Artificial &#34;arterio-venous&#34; permeable hollow fiber capillary system

ABSTRACT

An artificial “arterio-venous” permeable hollow fiber capillary membrane system for wound treatment is described, that can be placed onto a wound, under the wound dressing, to enable fluid-/mass exchange, and thus enables pH- and electrolyte regulation, the supply of factors/mediators/medications, the removal of secretion- and/or waste material, and the support of therapeutically applied cells in the wound.

FIELD OF THE INVENTION

The invention at hand pertains to active wound dressings for woundtreatment in medicine, e.g. of patients with burn disease or chronicskin wounds.

BACKGROUND

While injuries to the upper layer of the skin (epidermis, keratinocytes)can regenerate by themselves most of the time, larger deeper wounds thatreach the skin's regeneration layer (basal keratinocytes, progenitorcells) do not. The treatment of acute skin wounds, e.g. after burninjuries or chronic skin wounds, e.g. as a result of diabetes mellitusor peripheral circulatory disorders, is clinically not satisfactory.

Standard clinical therapy for larger skin wounds after wound cleaning issurgical autologous skin transplantation whereby a section of thepatient's own healthy skin is surgically removed, followed by thepreparation of a split skin-mesh transplant (where the to betransplanted skin is divided into a multitude of small areas), which islater transplanted on the wound area. However, autologous split-skin isoften not available in sufficient amounts, thus having to depend on thewound's self-healing ability under the wound dressing.

The method of choice for chronic skin disease is to keep the woundmoist/wet through regular misting and irrigating while the wounddressing is changed.

The purpose of the wound dressing in both applications is to reducefluid- and temperature loss as well as infection.

More sophisticated wound dressings include for example Integra, IntegraLife Science, USA or AlloDerm, LifeCell, USA, consisting of non-living,non-autologous cell cultures.

Methods for the removal of secretion from wounds are already known:Argenta, L. C., Morykwas, M. J. Vacuum assisted closure: A new methodfor wound control and treatment: Clinical experience. Annals of PlasticSurgery, 1997; 38(6): 563-77, or Joseph, E., et al.: A prospectiverandomized trial of vacuum assisted closure versus of chronicnon-healing wounds; Wounds, 2000; 12(3): 60-7.

A device for keeping the wound moist is also commercially available asWound V.A.C. Instill (Registered Trademark) from KCl, San Antonio, Tex.,USA. This device can be employed to alternately supply the wound withfluids and subsequently alternately remove fluids from the wound. Here,mass transfer does not occur as it occurs in an artificial capillarybed, but with significant central and irregular gradients, via a sharedinlet and outlet of a sponge in the center of the wound.

Carsin H. et al. and Phillips T. J. et al. and Still J. M. et al.published the early clinical results on keratinocyte transplantation.

The following are available commercialized skin replacements:Dermagraft-TC, by Advanced Tissue Sciences, USA, with live cells in formof sheets (extensive layers of connected cells), Organogenesis, USA,uses live human allogene fibroblasts and allogene keratinocyts in atwo-layer arrangement that is marketed by Novartis, C H as Apligraf.Genzyme, USA offers a service where autologous keratinocytes are removedfrom an area of the patient's healthy skin and passaged in a culturedish, and then placed on the wound as live cell sheets using fat gauzeas support structure. This method however, did not yield completelysatisfactory clinical results. For example, blistering on the wound sitelifts the cell sheets from the wound and significantly impairs cellsupply in the wound.

For these currently established techniques, the wound supply isunsatisfactory during wound healing, or the attachment rate of appliedcells. Problems include fluid-, electrolyte-, and pH displacements aswell as bacteria accumulation in the wound.

Should transplanted cells be used, this non-physiologic biomatix in thewound also prevents optimal cell growth and cell proliferation.

SUMMARY OF THE INVENTION

The purpose of the invention at hand is to introduce a device thatimproves mass exchange in the wound, including during the initialclinical phase of possible cell transplantation. The method/device,however, is suitable as an active wound dressing even without addingcells. The device can perfuse and supply the wound in a decentralfashion during continuous perfusion and thus provides conditions similarto an arterio-venous capillary bed, and facilitates drug-, mediator-,growth factor, and antibiotic/disinfectant perfusion, while enablingeven substance distribution, and optionally the generation of moderatenegative pressure. Likewise electrolyte- and pH-regulation can beperformed in the wound and continuous debris removal can be enabled. Amore open-porous arrangement enables a moist wound environment with theability to remove wound debris and/or bacteria or other germs.

BRIEF DESCRIPTION OF DRAWINGS

The invention at hand is further described with FIGS. 1 through 9.

FIG. 1: Problem of clinical application of in-vitro cultured cellssheets due to blister development, reducing the attachment rate of thecells. FIG. 1 a schematically shows the problem of clinical applicationof in-vitro propagated cell sheets 2) and the resulting blisterdevelopment (see arrow 1). FIG. 1 b shows how the blister (see arrow 1),expands during the attachment phase of the cell sheets 2) whichnegatively affects the adhering process of the cells to the skin. Whilea combination of such sheets with the invention at hand does not makesense, a combination, as described in FIG. 2, does. Wunde (German)=wound(English).

FIG. 2: Advantage of individually sprayed cells onto the wound, therebyavoiding blister development and facilitating an improved healingprocess. FIG. 2 a shows a design as it is shown in FIG. 1 b with ablister (1), FIG. 2 b shows the consequences when cells are sprayed ontothe wound (the cells 2 are marked with an arrow). The comparison ofFIGS. 2 a and 2 b demonstrates how blister development can be avoided byspraying the cells 2 onto the wound and thereby enabling improved woundhealing. A combination with the invention at hand makes sense. Wunde(German)=wound (English).

FIG. 3: Advantages of individual cells 2 sprayed onto the wound (FIG. 3a), which, in their function as progenitor cells, can heal significantlylarger wound areas. FIGS. 3 a and 3 b show a schematic comparison withcell sheet 2 application (FIG. 3 b) that are individually sprayed ontothe wound thereby, as progenitor cells, healing a significantly largerwound area. The cells are marked by an arrow (2). A combination with theinvention at hand makes sense. Wunde (German)=wound (English).

FIG. 4: A schematic illustration of an artificial capillary membranesystem that is connected to a surrounding that generates a firstindependent compartment (in the figure the not illustrated “wound”background), which depicts two additional hollow fiber arrangementsgenerating the independent compartments two (capillaries c), e) and h)and three (capillaries d), g) and f). The compartments two (referencesign 3) and three (reference sign 4) are each equipped with one inlet oroutlet and could perfuse the wound compartment one between the inletcompartment two and the outlet compartment three. The artificialcapillary membrane system in FIG. 4 corresponds with the portion of thesystem depicted under the wound dressing shown in FIG. 5, which islocated on top of the wound. The tube ends a) and b) (with in- outflowarrows) in FIG. 4 correspond with the tube ends in FIG. 6, named f). Thearrows in FIG. 7 correspond to point a) and b) in FIG. 4 respectively,or to f) and f2) in FIG. 6 respectively. The capillary membrane systemdepicted in FIG. 4 corresponds also to the illustration in FIG. 8 b.

FIG. 5: Anticipated clinical application of the artificial capillarysystem applied as active wound dressing (g, 10) with a fluid circulationsystem 8 and a pump system 7. Fluid is pumped from a reservoir 5 into acircuit (middle), a recirculation pump circulates the fluid to and fromthe capillary system 9 (shown in one arrangement in FIG. 4). A dischargepump pumps the fluids into an outlet reservoir 6. Negative or positivepressure can be generated in the wound compartment depending the speedsettings of the top and bottom pump in 7. Negative pressure enablesadditional removal of wound secretion and debris from the wound site.

Such an arrangement can also supply the wound in combination withsprayed cells (FIGS. 2 and 3) as well as support sprayed cells in thewound after spraying (FIG. 2).

The tube system running through the pump system on the right side of theillustration is described in FIG. 7.

FIG. 6: A particular arrangement of the tubes entering or exiting fromthe wound dressing, which enables sealing around tube between the skinb/ b2) and the sheeting a/ /a2 /h) above wound and artificial capillarysystem. The tubes f/ f2 exit from the wound b/ b2) and a seal betweenthe skin and the sheeting is enabled by the pad d/ d2) above which thetube f/ f2) exists the wound area through a hole c) in the sheet a/h).The cut between FIG. 6 a and FIG. 6 b illustrates an- in and outlet tubea) and b) in FIG. 4.

FIG. 7: The tubes in a perfusion system with three pumps 12), 13), 14)to operate a hollow fiber membrane system circuit 17), as described inFIG. 4). This tube system is depicted in FIG. 5 in another arrangement.Fluid is pumped from a reservoir (15) into a circuit (17), arecirculation pump 13) circulates the fluid to- and from the capillarysystem (right side of illustration). The arrows correspond to acapillary system shown in one arrangement in FIG. 4. An outlet pump 14)pumps fluid into an outlet reservoir (16). The arrows in FIG. 7 can leadto a) and b) in FIG. 4 or to f) and f2) in FIG. 6 respectively. Whilethe recirculation pump 13) controls the mass transfer form the circuitonto the wound, the top 12) and bottom pump 14) control the entire masstransfer from/to the patient. Negative or positive pressure can begenerated in the wound compartment depending the speed setting of thetop 12) and bottom pump 14). Negative pressure enables additionalremoval of wound secretion and debris from the wound site.

FIG. 8: Description of the application of a two-compartment artificialcapillary system (a) and a three-compartment system (b), and theapplication of a three-compartment arterio-venous artificial capillarysystem that enables perfusion or counter current perfusion (c) acrossthe wound.

FIG. 8 a corresponds with the illustration in FIG. 5; the configurationsin FIG. 8 c require a pump system whose circuit is illustrated in FIG.7. While figure (8 a) depicts a two-compartment system (the wound area,compartment one and capillary interior spaces are not depicted), FIG. 8b illustrates a three-compartment system; compartment one is the woundarea (not shown), compartment two is the lumen of the upper capillary,compartment three is the lumen of the bottom capillary. In thisarrangement, the compartments two and three are each equipped with aninlet (20) and outlet (21) that perfuse compartment one between inletcompartment two and outlet compartment three. The arrows symbolize thecounter current flow direction between compartment two and three.

FIG. 8 c also depicts the respective pumps (in- and outlet pumps 22, 23)as well as a medium inflow reservoir (24) and an medium outlet/wastereservoir (25).

FIG. 9: Combined application of a three-compartment “arterio-venous”artificial capillary system with hollow fiber capillary membranes (31,32) that create a second and third independent compartment in the woundand a sponge (30) for additional and separate removal of fluids, and/orsubstances, and/or bacteria out of the wound compartment one. The spongeallows to additionally and separately remove fluids, and/or substances,and/or bacteria via a separate pump (33) into separate waste reservoir(34). Here, mass transfer can be added by removing wound secretion anddebris via the sponge.

In addition to mass transfer and the option to generate a negativepressure, as described in FIGS. 4, 7, 8 b, 8 c, negative pressure canalso be generated in the wound, and/or wound secretion and debris can beadditionally removed. This configuration is also of interest to becombined with two-compartment capillary systems.

DESCRIPTION OF THE INVENTION

The invention described here provides an artificial capillary hollowfiber membrane system that can be placed into a first surrounding thatis creating an independent compartment, typically the wound environment,whereby the lumen of the artificial capillary system provides at least asecond independent compartment and encompasses at least one perfuseablehollow fiber capillary membrane arrangement. It can include a second, orfurther, independently perfuseable hollow fiber capillary membranearrangements that are forming a third-, or further, independentcompartments. According to the invention, the at least one independenthollow fiber capillary membrane arrangement is assembled of 1 to 1000hollow fibers, whereby the permeability limit is set for wound debris,and/or molecules of 500 to 2,000,000 MW cut off, preferably of 1,000 to900,000 MW cut off. The number of capillary membranes in the membranearrangements depends on the circumstances of the application and theconnections, meaning whether an arrangement is build with a lot ofcapillaries in parallel or a few capillaries in a meandering course. Incase of a meandering course one single capillary can already suffice,preferred are 1 to 100, preferably 1 to 50 and most preferred are 1 to10 hollow fiber capillaries. When using a parallel arrangement, thenumber of hollow fibers can be larger, between 3 and 1000, preferably 5to 600 and most preferred between 10 and 100 hollow fibers. Thereby eachhollow fiber capillary membrane arrangement consists of at least oneinlet and at least one outlet. Combinations of parallel arrangementswith meandering arrangements, and also duplication of severalarrangements, which may be connected via main in-/outflow tubes, can beadvantageous embodiments.

Because of the use of hollow fiber capillary membranes, the device canbe arranged and operated on top of uneven contours of a body. Specialcapillary arrangement, e.g., can be made for hands, ears, or the face.

To ensure the optimal supply and waste removal for the cells, it isadvantageous to provide two independent hollow fiber capillary membranearrangements to form a second- and a third independent compartment inthe wound. It is critical for the artificial arterio-venous permeablehollow fiber capillary system that even- and continuous mass transfer isprovided between the first independent compartment, which forms thesurroundings and at least one of further compartments. If aone-compartment hydrophilic capillary system is used, the flow is fromthe in- to the outlet; if a two-compartment system is used, the flow istypically in counter-current flow between two in/ and two outlets.Further compartments ad further functions, e.g. gas flow in a thirdhydrophobic oxygenation compartment. Even mass distribution is importantfor optimal supply of the wound, including for spray-transplanted skincells into the wound, as well as the removal of secretion and/or fluidsand/or debris out of the wound. In smaller wound systems, even andcontinuous mass transfer is enabled by a one-compartment capillarysystem, more even distribution in larger wounds by a two-compartmentcapillary system; resembling the functions of the arterial- and venouscapillaries in the natural tissue.

The inner diameter of the hollow fibers is preferably between 10 μm and2000 μm, most preferably between 40 μm and 800 μm.

According to the invention, other design forms are included in whichadditional hollow fiber capillary membrane arrangements formingindependent compartments can be instituted, e.g. for wound oxygenation.In the case where several independent hollow fiber capillary membranearrangements are utilized, each individual hollow fiber capillarymembrane can have one inlet and at least one outlet available or, someindependent compartments can share one inlet and one outlet.

With respect to materials and regarding the hollow fibers of the hollowfiber capillary membrane arrangements, the invention at hand containsall known state of the art natural or synthetic polymers or porousceramics that are used for hollow fibers (for example cellulose,polysulfone, polyethersulfone, polyamide or other synthetic or naturalpolymers) and/or adsorbeable/degradeable biomaterials, (includingcollagen and/or digestible cellulose), known in medical hollow fibermembrane technology.

Because of the arrangement of hollow fiber capillary membranes withcentral in-/outlets, the invention can be applied under a sterile wounddressing, e.g. skin wound dressing in form of a water impermeable foil,as known from surgical operation procedures. This preferred embodimentallows to keep the fluids in the wound.

With the invention at hand perfusion of solutions in the wound isenabled. These solutions include, e.g. physiologic electrolytessolutions (such as saline and buffer), nutrition (such as sugars andamino acids), drugs, antibiotics, growth factors, mediators,regeneration factors, dialysate solutions, irrigation solutions.

To support the perfusion via the inlet and/or outlets, the invention athand is equipped with at least one tube perfusion system—preferablydisposable—with a fluid supply bottle/bag and waste bottle/bag, operatedby e.g. gravity. Preferably, the tube system is operated by a pumpdevice, e.g. a roller pump device, for sterile disposable pump tubes. Ifone of the capillary compartments serves as oxygenator, the no less thanone inlet and/or outlet is connected to at least one gas supply. It isparticularly advantageous to apply fluid medium inlet pumps and/ormedium outlet pumps and/or medium circulation pumps, which can all beapplied in combination.

By means of the afore described modification of the invention at hand itis possible to arrange and operate the device in open perfusion mode.The invention at hand can also be arranged and operated in recirculationmode with a medium inlet shank and medium outlet shank. The describeddevice can alternatively be operated in counter current flow mode whenthe appropriate pump devices are installed.

The invention at hand can be further modified in such a way that thehollow fiber capillary membrane arrangement forming at least oneindependent compartment is, in addition, equipped with a pressurecontrol device, and/or flow control, and/or malfunction switch, and/ormedium warmer, and/or medium oxygenation, and/or probes for pressure,flow, PO₂, CO₂, Temperature, pH, electrolytes, glucose, lactate and/orcorresponding regulation units.

To support the suction of secretion, and/or fluids, and/or debris it isalso possible to apply the invention at hand under a sterile wounddressing in combination with a sponge connected to a suction system.Thus, secretion, and/or fluids, and/or debris can be removed, inaddition or separately, from the capillary compartments.

The hollow fiber capillary membrane arrangement can also be applied in asoft tissue wound as well as in the abdomen. In such a case, the hollowfiber capillary membrane arrangement can also be operated in combinationwith a sponge, which is equipped with an additional suction tube for theremoval of secretion, and/or fluids, and/or debris.

It is advantageous if additionally skin cells are applied prior toand/or during the wound treatment (FIGS. 2,3). In this case theinvention at hand supports for the treatment of skin defects with cellssince also cell supply can be enabled by the perfusate. It isadvantageous to apply the skin cells via a cell suspension through aspray head. The advantage of this is that the cells can be evenlydistributed across a larger area through the spray head, therebyenabling a larger transplant area (FIG. 2). Especially through the useof skin progenitor cells or stem cells, this combination yields asignificant enlargement of the possible therapeutic wound area (FIG. 3).It is advantageous that, using the invention at hand, cells can betemporarily supplied via the hollow fiber capillary membranearrangement.

The combination of the afore described cell spray method with thecapillary system according to the invention has multiple advantagescompared to state of the art technology, the skin wound treatment withapplication of cell sheets: confluent growing cells divide less, startproliferation later after transplantation, and exhibit less cellmigration activity. The combination has the advantage that the number ofin-vitro passages can be reduced and therefore cells expanded in-vitrocan be applied earlier, which reduces passage umbers and unwanteddifferentiation of basal keratinocytes (or skin progenitor cells) tokeratinocytes. An even earlier therapy begin can be enabled by sprayingintra-operative isolated skin cells, isolated and applied during thesame operation, with the combination of the artificial capillarymembranes. By avoiding in vitro culture, the basal keratinocytes cannotdifferentiate and, at the same time, due to the improved supply via theartificial capillaries the attachment and the supply of the cells thatwere temporarily impaired by the isolation process can be supported byfluid exchange in the wound. In a preferred method, the artificialcapillaries facilitate temporary support to the sprayed cells betweenthe wound and the outer wound dressing during the first treatment days.Nutrients, tempering, oxygenation, pH-regulation, electrolyte exchange,or detoxification as well as growth factors or antibiotics can also beapplied.

Example

Artificial capillaries were built—according to FIG. 4—in five versions:one in a 20×20 mm outer dimension “mat”, one in a 40×40 mm outerdimension “mat”, one in a 40×80 mm outer dimension “mat”, one in a40×120 mm outer dimension “mat”, and one in a 200×400 mm outer dimension“mat”. In each mat, hollow fiber capillaries of less than one millimeterin outer diameter (medical grade microporous polyether sulfoneplasmaseparation membranes, mPES, Akzo Membrana, Wuppertal, Germany)with a permeability limit for molecules of approximately 200,000 MWcut-of were arranged in parallel, with 5 capillaries per running 10 mmmof a “mat”. Thereby the 20×20 millimeter “mat”, e.g. contained 10parallel arranged capillaries of 20 milimeter length each. All ends offibers on one side of the mat were glued (Silastic, Dow Corning, USA)into 2 mm inner diameter silicone rubber tubes (Dow Corning, USA), wherepreviously small holes were punched for each matching point. Eachcapillary and each tube remained perfuseable after gluing. Thereby, each“mat” has an inflow tube system on one side and a tube outflow system onan opposite side, and the tubes represent common in-/or outflowdistribution tubes for all fibers (which are all arranged in parallel)in the “mat”. Two of these “mats” where overlaid and thus formed an“arterial-venous” capillary system. In each of those arrangements(containing two overlaid mats), each “mat” represents the lumen of oneindependent artificial capillary system, the second “mat” provided asecond compartment and the second “mat” provided a third independentperfusable compartment.

The flexibility of the capillary arrangement allowed an easy placementof the artificial capillary membrane system on body contours.

With the placement of hollow fiber capillary membranes under a foil, awater impermeable surgical operation wound incision foil, and the use ofsilicone rubber (Silastic, Dow Corning, USA) plates as described in FIG.6, the device could be sealed onto the skin and covered by a skin wounddressing. This arrangement allowed to keep the fluids in the compartmentbetween artificial capillaries and the skin and under the wounddressing.

To support the perfusion via the inlet and/or outlets, the device wasconnected via Luer-lock connectors (out of polystyrol) to a tubeperfusion system (poly-vinyl chloride, PVC, tubing), with a Luer-lockinfusion solution bag and a Luer-Lock waste container bag, as depictedin FIG. 7, and operated as depicted in FIGS. 5 and 8 c) with standardinfusion tube roller pumps.

1. An artificial capillary membrane system that is connected to a firstsurrounding/environment that is creating an independent compartment forwound treatment, thereby encompasses at least another, a second,independent compartment that is created by the lumen of an perfusablehollow fiber capillary membrane arrangement assembled of 1-2000(preferably 5-1000 and most preferably 10-100) hollow fibers with apermeability limit set for molecules of MW 500 to macromolecules and/orwound debris (preferably between MW 1,000 to 900,000 and most preferablyMW 1,000-50,000), whereby the no less than at least a second independentcompartment is created by a hollow fiber capillary membrane arrangementconsisting of hollow fibers arranged in parallel or in a meanderingcourse, and whereby each independent hollow fiber capillary membranecompartment is equipped with at least one inlet and one outlet, oralternatively is equipped with at least one shared inlet and one sharedoutlet, that is also arrangeable and operational on the contours ofuneven surfaces, e.g. the skin of a face, and/or in the abdomen, and/orin a soft tissue wound.
 2. A capillary system according to claim 1,thereby characterized that a hollow fiber capillary membrane arrangementis provided creating one-, two-, three-, and forth, additionalindependent compartments.
 3. A capillary system according to at leastone of the claims 1 to 2, thereby characterized that the hollow fibersof the hollow fiber capillary membrane arrangement are made ofpolysulfone, polyethersulfone, modified cellulose, polyamide or othersynthetic or natural polymers known to medical hollow fiber membranetechnology, and/or of resorbeable/digestible/degradable biomaterialsincluding collagen and cellulose, and that these exhibit an innerdiameter of 10 μm to 20,000 μm, preferably between 20 μm and 1000 μm andmost preferably between 40 μm and 800 μm.
 4. A capillary systemaccording to at least one of the aforementioned claims, therebycharacterized that the at least no less than one inlet and outlet of theat least one hollow fiber capillary membrane arrangement is connected toat least one pump device, exhibiting at least one fluid medium inletpump, and/or medium inlet pump, and/or medium outlet pump, and/or mediumcirculation pump, which may feature additional pressure control units,and/or flow control, and/or a malfunction control, and/or medium warmer,and/or medium oxygenation, and/or gas oxygenation provision, and/ormeasuring probes for pressure, flow, PO₂.CO₂, temperature, pH,electrolytes, glucose, lactate, and/or otherwise appropriate supplyand/or regulation units.
 5. A capillary system according to at least oneof the claims 1 to 4, thereby characterized that at least one of thehollow fiber membrane arrangements creating an independent compartmentis either arranged and operational in open perfusion mode, or in arecirculation circuit with medium inlet shank and medium outlet shank.6. A capillary system according to at least one of the claims 1 to 5,thereby characterized that at least a second of the additional hollowfiber membrane arrangements creating an independent compartment isarranged and operational in counter current flow mode.
 7. A capillarysystem according to at least one of the claims 1 to 6, therebycharacterized that at least a second of the additional hollow fibermembrane arrangements creating an independent compartment is arrangedand operational under a sterilizable wound dressing, e.g. skin wounddressing, e.g. in form of a operation skin incision foil for surgery. 8.A capillary system according to at least one of the claims 1 to 7,thereby characterized that at least a second of the additional hollowfiber membrane arrangements creating an independent compartment isoperational on/in a wound, whereby during continuous perfusion for masstransfer, lavage and/or drainage, a negative pressure is created by thepump system in the first compartment, and/or that secretion and/orbacteria and/or debris can be removed from the wound.
 9. A capillarysystem according to at least one of the claims 1 to 8, therebycharacterized that at least one of the hollow fiber membranearrangements creating an independent compartment is arranged andoperational in combination with a sponge in a wound, and/or in theabdomen, which is also equipped with an additional suction tube for theremoval of secretion, and/or fluid, and/or debris.
 10. A capillarysystem according to at least one of the claims 1 to 9, therebycharacterized that at least a second of the additional hollow fibermembrane arrangements creating an independent compartment is arrangedand operational on/in a wound in combination with a sponge, whereby thesponge is arranged in such a way that, during perfusion in othercompartments, a negative pressure is generated in the first compartmentand liquid/debris removal from the first (wound) compartment via thesponge is enabled.
 11. A method according to at least one of theaforementioned claims, for the utilization of at least one of the hollowfiber membrane arrangements creating an independent compartment asartificial capillary system for acute and/or chronic skin woundtreatment, soft tissue wound treatment, treatment of diseases/injuriesto the abdomen, and for mass exchange in the abdomen or body cavities.12. A method according to at least one of the aforementioned claims,thereby characterized that medium perfusion with antibiotics, growthfactors, mediators, regeneration factors, dialysate, buffers,electrolytes, irrigation solutions, oxygen carrier solution and/ornutrients, and/or gas perfusion with air, and/or oxygen, and/or gaseousmediators, including N═O, is performed, and/or that that warmth orcooling can be brought into the surrounding via these liquids or gasses.13. A method according to at least one of the aforementioned claims,thereby characterized that cells, including stem cells and/or autologousadult skin cells, and/or autologous skin progenitor cells, and/or fetalcells, and/or placenta cells, and/or homologous cells, and/orgene-technologically modified cells, are imported to the wound. e.g. byspray-transplantation, prior to and/or during capillary membranearrangement perfusion, and that the cells are temporarily feed/suppliedvia the hollow fiber capillaries to enable tissue engineering in thewound.
 14. A method according to at least one of the aforementionedclaims, thereby characterized that the hollow fiber capillary membranearrangement is applied in combination with a flat membrane in such a waythat the artificial capillary removal is simplified after remaining inthe wound for extended period of time.
 15. A method according to atleast one of the aforementioned claims, thereby characterized that thehollow fiber capillary membrane arrangement is applied as temporaryextracorporeal or intracorporeal organ support, for skin regeneration,for wound closure, to support blood circulation for and/or to regeneratewound vessels, and/or to provide a physiological environment.
 16. Amethod according to at least one of the aforementioned claims, therebycharacterized that a hollow fiber capillary membrane arrangement isapplied which will disintegrate, be resorbed, and/or be digested in situafter utilization.
 17. A method according to at least one of theaforementioned claims, thereby characterized that a hollow fibercapillary membrane arrangement serves as abdominal lavage, and/ordrainage, and/or irrigation.
 18. A method according to at least one ofthe aforementioned claims, thereby characterized that a hollow fibercapillary membrane arrangement serves for use in the abdomen asperfusion system for blood-independent mass exchange with extracorporealorgan support systems to- and from the patients plasma via the serosa ofthe intestinal tissue.
 19. A method according to at least one of theaforementioned claims, thereby characterized that a hollow fibercapillary membrane arrangement serves as enzymatically degradablepolymer/synthetic-capillary system in regenerative medicine applicationsto address the lack of a vascular structure within tissue engineeredconstructs for implantation, for support of the implanted cells and topromote formation of a host originated vascular system in the tissueengineered implanted organ, by connecting to oxygen and nutrient sourcesand angiogenic factors externally, followed by dissolving timely plannedusing an enzyme solution provided through the external connect.